Journal of Intercultural Ethnopharmacology

Mini Review

www.jicep.com
DOI: 10.5455/jice.20160331064836

The consumption of propolis and royaljelly in preventing upper respiratory
tract infections and as dietary
supplementation in children
Sevda Yuksel1, Sumeyya Akyol2
Department of Child
Development, Schoolof Health, Turgut Ozal
University, Ankara,
Turkey, 2Department ofMedical Biology, Facultyof Medicine, Turgut Ozal
University, Ankara, Turkey

1Address for correspondence:
Sevda Yuksel, Department ofChild Development, Schoolof Health, Turgut Ozal
University, Ankara, Turkey.
E-mail: sevdayuksel@gmail.
com
Received: March 22, 2016
Accepted: March 31, 2016
Published: March 31, 2016

ABSTRACT
Propolis and royal jelly (RJ), two important honeybee products, have been used commonly all over the world
as traditional and ethnopharmacological nutrients since ancient times. Both of them have a lot of active
ingredients which are known to be effective for several medical conditions. In this article, medical databases
were searched for the usage of RJ and propolis in upper respiratory tract infections (URTI) and as a dietary
supplementation, together and separately. 10-hydroxy-2-decenoic acid is the most prominent active compoundshowing antimicrobial effect within RJ. Caffeic acid phenethyl ester is the most famous one that shows
antimicrobial and anti-inflammatory effect within propolis. When compared with propolis, RJ was found to havericher content for all three main nutrients; proteins, carbohydrates, and lipids. More clinical, experimental, andbasic studies are needed to find out the best standardized mixture to cope with URTI in which RJ and propolis
will be main ingredients in addition to the other secondary compounds that have health-beneficial effects.

KEY WORDS: 10-hydroxy-2-decenoic acid, caffeic acid phenethyl ester, infections, nutrition, propolis, respiratory
tract, royal jelly

INTRODUCTION

REVIEW METHODOLOGY

The term “herbal medicine” has been used to identify thetherapeutic plants or particular substances derived from theplants to support the body to fight against various diseases
including infections or improving overall health. The utilizationof complementary and alternative medicine (CAM) products insuch type of infections is very popular. The similar things canbe brought forward for nutritional usage of phytotherapeutic
products as well. Two honeybee products, propolis and royaljelly (RJ), have been used commonly all over the world astraditional and ethnopharmacological nutrients since ancient
times. Both of them have a lot of active ingredients which
are known to be effective for several medical conditions. For
example, caffeic acid phenethyl ester (CAPE) from propolisis thought to be responsible well-known effects of propolis
including anticancer, antioxidant, immune-modulatory,
antibacterial, antiviral, and anti-inflammatory [1]. As a lipid
soluble antioxidant, CAPE has been used in a number of
inflammatory and infectious diseases as traditional medicine[2]. 10-hydroxy-2-decenoic acid (10-HDA) from RJ has also
several activities such as protective and therapeutic effects on
infections and has nutritious properties [3].

Literature searches from PubMed, Medline, Scopus, ScopeMed,
and Google Scholar were performed to find out the publishedarticles about the topic to identify the nutritional value of
propolis and RJ and the usage of them in upper respiratory tract
infections (URTI). All articles written in English or having justan English abstracts were analyzed up to March 2016. Databases
were searched for RJ in URTI, propolis in URTI, RJ in nutritional
requirements, and propolis in nutritional requirements. As asecond step, these parameters were combined for two mixturesand searched for new compounds or mixtures being used forthe same purposes. If there is no actual contemporary review ororiginal articles, older ones were considered to reach a reliableconclusion.

308

PROPOLIS
General Information
It is a mixture produced by honeybee after processes within his
saliva. This product is used by the bees to protect their hives
from infected single cells such as fungi and bacteria to moisture
J Intercult Ethnopharmacol ● 2016 ● Vol 5 ● Issue 3

Yuksel and Akyol: Propolis and royal jelly in infection

and stabilize temperature within the hives, and to embalm theforeign materials and to repair all the cracks within the hives [4].
A study revealed the presence of 60 different important
phytochemicals in methanolic extract of Nigerian bee propolis
including phlobatannins, glycosides, tannins, anthraquinones,
steroids, saponins, flavonoids, and alkaloids [5]. This greenishbrown and sticky product has different mixtures dependingon what flowers and trees they accessed to and the place ofthe bees [6]. It has been claimed that every single moleculeof propolis needs to be studied to show the source of the realeffect and the underlying mechanism of these effects [6]. Akyol
et al. suggested that the clinical importance of CAPE stems not
only from free radical scavenging and antioxidant activities, butalso by marked nuclear factor-κB (NF-κB), nitric oxide synthaseactivity, and apoptosis inhibition together with the suppressionof caspase-3 activities and p38 phosphorylation [7].

in the digestive utilization of magnesium, iron calcium, andphosphorus [14].

RJ
General Information
RJ is a mix of yellow-white creamy and acidic secretion
produced by the worker honeybees using their mandibular andhypopharingeal glands to supply a principal food for queen
honeybee. It is a nutritive secretion rich in minerals, vitamins,
carbohydrates, and proteins [15]. It has a lot of minerals(mainly calcium and iron), vitamins (mainly riboflavin, niacin,
thiamin), fatty acids, sugars, proteins, and free amino acids.
Many important activities of RJ have been attributed to its oneof active contents, 10-HDA.

The Antimicrobial Effects

The Antimicrobial Eﬀects

Lately, antiviral features of CAPE have been reviewed byscientists suggesting CAPE and its targets may have been
regarded as a new field to design new therapeutics [8]. The
other goal of that study was to understand the molecularmechanism of virus-related diseases. Propolis was tested forexperimental Pseudomonas aeruginosa keratitis in rabbits
and found that it can be regarded as a useful supplemental
compound but should not be considered as a substitute fora contemporary antibiotic cure for this type of keratitis [9].
A mixture of ethanolic extract of propolis (EEP) was found to
inhibit viridans Streptococci and regarded as an antimicrobial
compound [10]. On the other hand, several different propolis
samples were found to have noteworthy antimicrobial activities
against yeasts and Gram-positive bacteria [11]. It has beenfound to be effective on fungi as well [12]. All oral candidiasis
patients administered to standardized propolis extract
exhibited a significant lesion suppression comparable to thosetreated with nystatin [12].

There seems to be some evidence of a possible role of RJ in
infections, but the evidence even now inadequate to accept
suggestions for medical care of children with respiratory
tract infections. Four antimicrobial peptides were isolated
and sequenced by quadrupole-time-of-flight tandem mass
spectrometry: PFKLSLHL-NH2 (Jelleine 1), TPFKLSLHL-NH2(Jelleine 2), EPFKLSLHL-NH2 (Jelleine 3), and TPFKLSLHNH2 (Jelleine 4) from RJ and noticed that some of them
have antimicrobial properties against yeast, Gram-negativeand Gram-positive bacteria [16,17]. There are very short
peptides presenting hydrophobic sequences. RJ exhibits
bacteriostatic [18] and antimicrobial activities [19] just becauseof the acidic content, organic acids and proteins (mainly
known as royalisin) it has. Sver et al. found that RJ exhibits
immune-modulatory features by stimulating immune-co-potent
cell proliferation and production of antibodies in mice or by
reducing humoral immune functions in rats [20].

The Value of Propolis as Dietary Supplement
Many investigations have been conducted to evaluate theeffectiveness of propolis on experimentally induced diabetes
including antidiabetic properties of Nigerian propolis [13]. The
study indicated that EEP could benefit hypertriglyceridemia,
hypercholesterolemia, and hyperglycemia along with keeping
safe pancreas and liver against alloxan-induced diabetes in termsof biochemical and histological parameters [13].
The effectiveness of bee propolis on physical fitness and someother parameters were investigated after adding it to the food asa supplementation in rats [14]. Improved regeneration efficiencyof hemoglobin, increased calcium and phosphorus absorption,
improved utilization of iron, and increased weight gain were
notified in the rats fed with propolis. In an experimental study,
propolis and/or multifora pollen was found to be beneficial
as co-adjuvants in the medical care of nutritional ferropenic
anemia; supplemented the regular foods of rats with propolis
and/or multifora pollen caused to a considerable amelioration
J Intercult Ethnopharmacol ● 2016 ● Vol 5 ● Issue 3

The Value of RJ as Dietary Supplement
RJ was investigated for its supplemental value that can enhanceathletic performance which can also give an idea for its supportingrole to human well-being without classifying those adults andchildren [21]. Most of the health-protecting properties of RJ
have been attributed, at least in part, to actions of lipids foundin RJ [22]. A possible beneficial effect of fresh RJ was reported inmice in terms of recovery from swimming to exhaustion [23]. No
other effects of RJ were found in exercise but it was found to beeffective on new bone formation and rapid maxillary expansion,
which shows its valuable support to the general condition of the
body [24]. Epidermal hydration, maintained by the epidermal
lipid barrier, of which ceramide is one of the constituents, hasbeen enhanced by dietary supplementation of RJ in mice [25].
The effects of RJ and CAPE on aggrecanases in chondrosarcoma
cells were investigated to enlighten the molecular basis of thesecompounds in osteoarthritis [26]. interleukin-1 alpha (IL-1α)
was used to induce the cells. 10-HDA has been well known tohave an activity to promote collagen production. It was shownthat these compounds could block the NF-κB cascade, which309

Yuksel and Akyol: Propolis and royal jelly in infection

is very important in osteoarthritis pathogenesis, which in turnmight give estimation about the prevention of infections [27].
On the other hand, RJ has been suggested to support brain levelsof dopamine in male bees, showing, in turn, the importance oftyrosine amino acids taken by nutritious supplements such as
RJ [28].

MIXTURE OF PROPOLIS, RJ AND OTHER CAM
PRODUCTS
Echinacea, a common immune-stimulant, is very well known
as an anti-inflammatory and antioxidant product as well. Someclinical studies have shown that Echinacea could intensify the
production of cytokines including tumor necrosis factor-α,IL-10, IL-6, and IL-1 by macrophages [29]. The effectivenessof a preparation containing propolis, vitamin C, and Echinacea
extract for URTI in young children was investigated in arandomized, double-blind, and placebo-controlled study
with a 3 months follow-up time interval [30]. The number ofchildren who affected from URTI, the total number of disease
episodes, and the mean number of episodes per child were
found significantly lower. The total number illness days andduration of episodes were also lower compared to placebo group.
According to this clinical study, the days affected by fever, theusage of antipyretics and antibiotics, the numbers of physician
visits for URTI was significantly lower [30]. The positive effectof combination of Echinacea, propolis and vitamin C in URTI
in children was reviewed by another study showing decrease thenumber of episodes, the duration of symptoms, and the numberof days of illness [31].
There are several studies showing bee products to haveantibacterial, antiviral and anti-inflammatory features [32],especially for the prevention of URTI [33]. Henatsch
et al. overviewed of the effectiveness beehive products in
otorhinolaryngology [34]. What they found is propolis might
be used in safe in the medical care of acute otitis media, mouth
ulcer, and stomatitis, while RJ could safely be used to reduce
mucositis.

SELECTED THERAPEUTICAL EXPERIENCES
Due to the fact that foods ingested may influence attention,
moods, emotion and cognition of children, there is growing
evidence that parents are more inclined to use dietary
supplements for their children [35]. Children more commonly
take bee propolis as dietary supplement possibly due to theparental encouragement for children to prevent colds and flu
and strengthen the immune system [36]. Propolis was foundto be the fifth one within the top five supplements consumed
among elementary school children in Taiwan [35].

CONCLUSION
Reviewing of the scientific reports on RJ and propolis could
help us to reach two main conclusions in terms of nutritional
properties and the usage of these mixtures in URTI as remedial
agents: First, no published evidence reach a level that scientists
310

and public accept the exact supportive role of these two CAM.
Still there is a tremendous need for advanced good quality
experimental and clinical studies. Second, placebo-controlled,
randomized, double-blinded, and high-quality studies on thesafety and efficacy of herbal therapy, especially for the mixtureof propolis, RJ, and Echinacea in URTI are needed. Thereis obviously an urgent need to find out the best reliable andstandardized mixture, which have been approved for healthbeneficial effects such as propolis, RJ, Echinacea for children
to cope with seasonal URTI as an alternative option in addition
to classical treatment modalities.

REFERENCES
1.

2.

3.

4.
5.
6.
7.
8.
9.

10.
11.
12.
13.

14.

15.
16.

17.

Natarajan K, Singh S, Burke TR Jr, Grunberger D, Aggarwal BB. Caffeic
acid phenethyl ester is a potent and specific inhibitor of activationof nuclear transcription factor NF-kappa B. Proc Natl Acad Sci U S A
1996;93:9090-5.
Akyol S, Akbas A, Butun I, Toktas M, Ozyurt H, Sahin S, et al. Caffeic
acid phenethyl ester as a remedial agent for reproductive functions
and oxidative stress-based pathologies of gonads. J Intercult
Ethnopharmacol 2015;4:187-91.
Takikawa M, Kumagai A, Hirata H, Soga M, Yamashita Y, Ueda M,
et al. 10-Hydroxy-2-decenoic acid, a unique medium-chain fatty acid,activates 5’-AMP-activated protein kinase in L6 myotubes and mice.
Mol Nutr Food Res 2013;57:1794-802.
Akyol S, Armutcu F, Yigitoglu MR. The medical usage of caffeic
acid phenethyl ester (CAPE), an active compound of propolis, inneurological disorders and emergencies. Spatula DD 2011;1:37-42.
Lawal B, Shittu OK, Abubakar AN, Olalekan IA, Jimoh AM,
Abdulazeez AK. Drug leads agents from methanol extract of Nigerianbee (Apis mellifera) propolis. J Intercult Ethnopharmacol 2016;5:43-8.
Akyol S, Gulec MA, Erdemli HK, Akyol O. Can propolis and caffeic
acid phenethyl ester be promising agents against cyclophosphamide
toxicity? J Intercult Ethnopharmacol 2016;5:105-7.
Akyol S, Erdemli HK, Armutcu F, Akyol O. In vitro and in vivo
neuroprotective effect of caffeic acid phenethyl ester. J Intercult
Ethnopharmacol 2015;4:192-3.
Erdemli HK, Akyol S, Armutcu F, Akyol O. Antiviral properties ofcaffeic acid phenethyl ester and its potential application. J Intercult
Ethnopharmacol 2015;4:344-7.
Onlen Y, Tamer C, Oksuz H, Duran N, Altug ME, Yakan S. Comparative
trial of different anti-bacterial combinations with propolis andciprofloxacin on Pseudomonas keratitis in rabbits. Microbiol Res
2007;162:62-8.
Tichy J, Novak J. Detection of antimicrobials in bee products withactivity against viridans streptococci. J Altern Complement Med
2000;6:383-9.
Uzel A, Sorkun K, Onçag O, Cogulu D, Gençay O, Salih B. Chemicalcompositions and antimicrobial activities of four different Anatolian
propolis samples. Microbiol Res 2005;160:189-95.
Santos VR, Pimenta FJ, Aguiar MC, do Carmo MA, Naves MD,
Mesquita RA. Oral candidiasis treatment with Brazilian ethanol
propolis extract. Phytother Res 2005;19:652-4.
Babatunde IR, Abdulbasit A, Oladayo MI, Olasile OI, Olamide FR,
Gbolahan BW. Hepatoprotective and pancreatoprotective properties ofthe ethanolic extract of Nigerian propolis. J Intercult Ethnopharmacol
2015;4:102-8.
Haro A, López-Aliaga I, Lisbona F, Barrionuevo M, Alférez MJ,
Campos MS. Beneficial effect of pollen and/or propolis on themetabolism of iron, calcium, phosphorus, and magnesium in rats withnutritional ferropenic anemia. J Agric Food Chem 2000;48:5715-22.
Palma MS. Composition of freshly harvested Brazilian Royal Jelly:
Identification of carbohydrates from the sugar fraction. J Apicult Res
1992;31:42-4.
Fontana R, Mendes MA, de Souza BM, Konno K, César LM,
Malaspina O, et al. Jelleines: A family of antimicrobial peptides
from the Royal Jelly of honeybees (Apis mellifera). Peptides
2004;25:919-28.
Brudzynski K, Sjaarda C. Honey glycoproteins containing antimicrobial

J Intercult Ethnopharmacol ● 2016 ● Vol 5 ● Issue 3

Yuksel and Akyol: Propolis and royal jelly in infection

18.

19.
20.
21.

22.
23.
24.
25.
26.

27.

28.

peptides, Jelleins of the Major Royal Jelly Protein 1, are responsible
for the cell wall lytic and bactericidal activities of honey. PLoS One
2015;10:e0120238.
Fujiwara S, Imai J, Fujiwara M, Yaeshima T, Kawashima T,
Kobayashi K. A potent antibacterial protein in royal jelly. Purificationand determination of the primary structure of royalisin. J Biol Chem
1990;265:11333-7.
Chu LK, Liu TM, Ho KK. Growth inhibition of Ascosphaera apis byroyal jelly and 10-hydroxy-2-decenoic acid. Bull Inst Zool Acad Sin(Taipei) 1992;31:73-9.
Sver L, Orsolic N, Tadic Z, Njari B, Valpotic I, Basic I. A royal jelly as
a new potential immunomodulator in rats and mice. Comp Immunol
Microbiol Infect Dis 1996;19:31-8.
King DS, Baskerville R, Hellsten Y, Senchina DS, Burke LM, Stear SJ,
et al. A-Z of nutritional supplements: Dietary supplements, sports
nutrition foods and ergogenic aids for health and performancePart 34. Br J Sports Med 2012;46:689-90.
Li X, Huang C, Xue Y. Contribution of lipids in honeybee (Apis mellifera)
royal jelly to health. J Med Food 2013;16:96-102.
Kamakura M, Mitani N, Fukuda T, Fukushima M. Antifatigue effect offresh royal jelly in mice. J Nutr Sci Vitaminol (Tokyo) 2001;47:394-401.
Özan F, Çörekçi B, Toptas O, Halicioglu K, Irgin C, Yilmaz F, et al. Effectof Royal Jelly on new bone formation in rapid maxillary expansion in
rats. Med Oral Patol Oral Cir Bucal 2015;20:e651-6.
Jeon S, Cho Y. Epidermal hydration is improved by enhanced ceramide
metabolism in aged C57BL/6J mice after dietary supplementation ofRoyal Jelly. J Med Food 2015;18:999-1006.
Jung WK, Choi I, Lee DY, Yea SS, Choi YH, Kim MM, et al. Caffeic
acid phenethyl ester protects mice from lethal endotoxin shock andinhibits lipopolysaccharide-induced cyclooxygenase-2 and inducible
nitric oxide synthase expression in RAW 264.7 macrophages via
the p38/ERK and NF-kappaB pathways. Int J Biochem Cell Biol
2008;40:2572-82.
Akyol S, Acar M, Unal ZN, Hasgul R, Erdogan S, Demircan K, et al.
The effects of caffeic acid phenethyl ester (CAPE), royal jelly, andcurcumin on gene expression of ADAMTS-1, -5, and -9 in OUMS-27
chondrosarcoma cells: A preliminary study. Ann Paediatr Rheum
2013;2:27-37.
Sasaki K. Nutrition and dopamine: An intake of tyrosine in royal jelly

J Intercult Ethnopharmacol ● 2016 ● Vol 5 ● Issue 3

can affect the brain levels of dopamine in male honeybees (Apismellifera L.). J Insect Physiol 2016;87:45-52.
29. Burger RA, Torres AR, Warren RP, Caldwell VD, Hughes BG.
Echinacea-induced cytokine production by human macrophages.
Int J Immunopharmacol 1997;19:371-9.
30. Cohen HA, Varsano I, Kahan E, Sarrell EM, Uziel Y. Effectiveness ofan herbal preparation containing Echinacea, propolis, and vitamin C
in preventing respiratory tract infections in children: A randomized,
double-blind, placebo-controlled, multicenter study. Arch Pediatr
Adolesc Med 2004;158:217-21.
31. Carr RR, Nahata MC. Complementary and alternative medicine forupper-respiratory-tract infection in children. Am J Health Syst Pharm
2006;63:33-9.
32. Viuda-Martos M, Ruiz-Navajas Y, Fernández-López J, Pérez-Alvarez JA.
Functional properties of honey, propolis, and royal jelly. J Food Sci
2008;73:R117-24.
33. Trumbeckaite S, Dauksiene J, Bernatoniene J, Janulis V. Knowledge,
attitudes, and usage of apitherapy for disease prevention andtreatment among undergraduate pharmacy students in Lithuania.
Evid Based Complement Alternat Med 2015;2015:172502.
34. Henatsch D, Wesseling F, Kross KW, Stokroos RJ. Honey and beehive
products in otorhinolaryngology: A narrative review. Clin Otolaryngol
2015.
35. Chen SY, Lin JR, Kao MD, Hang CM, Cheng L, Pan WH. Dietary
supplement usage among elementary school children in Taiwan:
Their school performance and emotional status. Asia Pac J Clin Nutr
2007;16 Suppl 2:554-63.
36. Takagi Y, Choi IS, Yamashita T, Nakamura T, Suzuki I, Hasegawa T,
et al. Immune activation and radioprotection by propolis. Am J Chin
Med 2005;33:231-40.
© SAGEYA. This is an open access article licensed under the termsof the Creative Commons Attribution Non-Commercial License (http://
creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted,
noncommercial use, distribution and reproduction in any medium, provided
the work is properly cited.
Source of Support: Nil, Conﬂict of Interest: None declared.

311